POS0850 THE EFFECT OF PERIOPERATIVE JANUS KINASE INHIBITOR WITHDRAWAL ON SURGICAL SITE INFECTION AND FLARE OF RHEUMATOID ARTHRITIS IN ORTHOPEDIC SURGERY: A MULTI-CENTER OBSERVATIONAL STUDY
Authors: T. Yoshida, A. Onishi, Y. Hasegawa, R. Yanai, S. Takanashi, S. Fukui, S. Watanabe, L. Hirahara, A. Morinobu
Journal: Annals of the Rheumatic Diseases (2023)

Background To prevent surgical site infection (SSI), recent guidelines recommend a 3-day preoperative withdrawal of Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients durling orthopedic surgery [1]. However, there is still insufficient evidence to support this practice. On the other hand, RA flare associated with JAKi withdrawal is also an important outcome, and an appropriate withdrawal period is crucial. Objectives We conducted a multicenter observational study to investigate the effect of the perioperative JAKi withdrawal period on SSI and RA flares in orthopedic surgery. Methods Patients with RA who visited six tertiary care centers between 2018 and 2021 and underwent JAKi before orthopedic surgery were included. We defined SSI based on the United States Centers for Disease Control criteria and flare as the clinician-assessed newly appearing or worsening joint pain or swelling during JAKi discontinuation. Results Of 30 patients, 23 (76.7%) patients withdrew JAKi. More than half of the patients withdrew JAKi 1 day before surgery or continued it (16/30, 53.3%). The median preoperative and postoperative JAKi withdrawal periods were 1 day (interquartile ranges [IQR]: 0–3.3) and 4.5 days (0.8–11.8), respectively. Two patients (6.7%) developed SSI. Both had multiple risk factors for SSI (Figure 1). Seven out of 30 patients flared (23.3%). The postoperative withdrawal period of JAKi was significantly associated with flares (odds ratio [OR] for &gt; 14 days compared to ≤ 7 days: 8.5, 95% confidence interval [CI]: 0.97–74.4, p = 0.048) (Table 1). The risk of RA flare increased by 15% for each postoperative withdrawal day of JAKi (OR [95%], 1.15 [1.00–1.34], p = 0.01). Conversely, the preoperative withdrawal period was not associated with flare (OR for ≥ 4 days compared to ≤ 1 day: 3.25, 95% CI: 0.46–22.9, p = 0.24). Conclusion Real-world data showed the incidence of SSIs is low, despite the fact that a large percentage of patients have been withdrawn JAKi one day prior to surgery or continued it. Patients who developed SSI had multiple risk factors regardless of the perioperative JAKi withdrawal period. Considering the risk factors for SSI, shortening the postoperative JAKi withdrawal period may be essential to prevent RA flares. Reference [1]Goodman SM, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheumatol Hoboken NJ. 2022;74:1464–73. Figure 1. Risks of surgical site infection Table 1. Unadjusted odds ratio of risk of flares of rheumatoid arthritis Patients with flare (n=7) Patient without flare (n=23) Unadjusted OR (95% CI) p-value Female, n (% ) 7 (100 ) 20 (87 ) not estimated Age, years, median [IQR] 69 [59, 76] 73 [59, 79] 1.00 (0.93–1.08 ) 1.00 Disease duration, years, median [IQR] 17.5 [10.6, 21.5] 18.6 [11.7, 25.1] 0.95 (0.86–1.06 ) 0.30 DAS (CRP), median [IQR] 3.05 [2.61, 4.60] 2.41 [2.09, 3.37] 2.23 (0.66–7.53 ) 0.18 MTX dose, median [IQR], (mg ) 6 [0, 8] 6 [0, 8] 1.02 (0.80–1.29 ) 0.90 PSL dose, median [IQR], (mg ) 3 [0, 5] 2 [0, 4] 1.24 (0.89–1.73 ) 0.20 Total JAK inhibitor withdrawal days, median [IQR] 15 [9, 34] 4 [0, 11] 1.13 (1.00–1.27 ) 0.01 ≤ 7 days, n (% ) 1 (14.3 ) 14 (60.9 ) Reference 8–14 days, n (% ) 1 (14.3 ) 5 (21.7 ) 2.80 (0.15–53.7 ) 0.50 ≥ 15 days, n (% ) 5 (71.4 ) 4 (17.4 ) 17.50 (1.56–196.3 ) 0.01 Pre-operative withdrawal days, median [IQR] 3 [1, 6] 1 [0, 3] 1.23 (0.88–1.71 ) 0.23 ≤ 1 day, n (% ) 3 (42.9 ) 13 (56.5 ) Reference 2–3 days, n (% ) 1 (14.3 ) 6 (26.1 ) 0.72 (0.06–8.46 ) 0.79 &gt; 4 days, n (% ) 3 (42.9 ) 4 (17.4 ) 3.25 (0.46–22.9 ) 0.24 Post-operative withdrawal days, median [IQR] 14 [5, 28] 3 [0, 8] 1.15 (1.00–1.34 ) 0.01 ≤ 7 days, n (% ) 2 (28.6 ) 17 (73.9 ) Reference 8–14 days, n (% ) 2 (28.6 ) 3 (13.0 ) 5.67 (0.56–57.2 ) 0.15 ≥ 15 days, n (% ) 3 (42.9 ) 3 (13.0 ) 8.50 (0.97–74.4 ) 0.048 Surgical invasion degree (moderate to severe), n (% ) 2 (28.6 ) 14 (60.9 ) 0.26 (0.04–1.62 ) 0.15 Acknowledgements: NIL. Disclosure of Interests Tsuneyasu Yoshida: None declared, Akira Onishi: None declared, Yasuhiro Hasegawa: None declared, Ryo Yanai: None declared, Satoshi Takanashi: None declared, Sho Fukui: None declared, Shinji Watanabe: None declared, Lisa Hirahara: None declared, Akio Morinobu Speakers bureau: Speaker’s bureau from Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K., Eisai Co. Ltd., Bristol-Myers Squibb., Mitsubishi Tanabe Pharma Co., and Astellas Pharma Inc. and grant/research support from Asahi Kasei Pharma Corp., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co. Taisho Pharmaceutical Co., Ltd. and Eisai Co. Ltd. outside the work.